Programmed cell death by apoptosis is a major mechanism for regulating cell number and tissue homeostasis. Apoptosis is tightly controlled through the action of both activators and inhibitors of caspases. One family of caspase inhibitors is the Inhibitors of Apoptosis Proteins (IAP). IAP contain 1-3 baculoviral IAP repeat (BIR) domains, which directly interact with caspases and inhibit their apoptotic activity. XIAP is an IAP protein.
ARTS is a pro-apoptotic protein derived by differential splicing from the human septin H5/PNUTL2/CDCrel-2a (Sept4) gene. ARTS contains a P-loop GTP-binding motif conserved in the Sept family. Yet unlike most other Sept family members, it is localized to mitochondria and promotes apoptosis via TGF-beta and other pro-apoptotic stimuli, such as etoposide, arabinoside (ara-C), staurosporine and Fas. A number of types of cancer and neoplastic cells lack ARTS protein expression and/or activity.
Methods for inducing apoptosis in cells, for example neoplastic or cancer cells, are needed for therapeutic applications for a wide range of diseases. In addition, methods for inhibiting excessive or aberrant apoptosis in cells are needed for therapeutic applications for a different major class of diseases.